FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children’s Oncology Group trial AALL0631
| Autor: | Joanne M. Hilden, Mignon L. Loh, Stephen P. Hunger, Lia Gore, Elizabeth A. Raetz, Naomi J. Winick, William L. Carroll, Donald Small, John A. Kairalla, Cindy Wang, Wanda L. Salzer, Nyla A. Heerema, Zo Ann E. Dreyer, Meenakshi Devidas, Michael J. Borowitz, Andrew J. Carroll, Patrick A. Brown |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty medicine.medical_treatment Carbazoles Article 03 medical and health sciences 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Furans Protein Kinase Inhibitors Chemotherapy biology business.industry Lestaurtinib Infant Histone-Lysine N-Methyltransferase Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Infant Acute Lymphoblastic Leukemia Leukemia 030104 developmental biology KMT2A fms-Like Tyrosine Kinase 3 030220 oncology & carcinogenesis Pharmacodynamics biology.protein Female FLT3 Inhibitor business Myeloid-Lymphoid Leukemia Protein Ex vivo medicine.drug |
| Zdroj: | Leukemia |
| Popis: | Infants with KMT2A‐rearranged acute lymphoblastic leukemia (KMT2A-r ALL) have a poor prognosis. KMT2A-r ALL overexpresses FLT3, and the FLT3 inhibitor (FLT3i) lestaurtinib potentiates chemotherapy‐induced cytotoxicity in preclinical models. Children’s Oncology Group (COG) AALL0631 tested whether adding lestaurtinib to post‐induction chemotherapy improved event-free survival (EFS). After chemotherapy induction, KMT2A-r infants received either chemotherapy only or chemotherapy plus lestaurtinib. Correlative assays included FLT3i plasma pharmacodynamics (PD), which categorized patients as inhibited or uninhibited, and FLT3i ex vivo sensitivity (EVS), which categorized leukemic blasts as sensitive or resistant. There was no difference in 3-year EFS between patients treated with chemotherapy plus lestaurtinib (n = 67, 36 ± 6%) vs. chemotherapy only (n = 54, 39 ± 7%, p = 0.67). However, for the lestaurtinib-treated patients, FLT3i PD and FLT3i EVS significantly correlated with EFS. For FLT3i PD, EFS for inhibited/uninhibited was 59 ± 10%/28 ± 7% (p = 0.009) and for FLTi EVS, EFS for sensitive/resistant was 52 ± 8%/5 ± 5% (p |
| Databáze: | OpenAIRE |
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